PMID- 28751099
OWN - NLM
STAT- MEDLINE
DCOM- 20180220
LR  - 20220409
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 39
IP  - 8
DP  - 2017 Aug
TI  - Efficacy and Safety of Delayed-release Dimethyl Fumarate for Relapsing-remitting 
      Multiple Sclerosis in Prior Interferon Users: An Integrated Analysis of DEFINE 
      and CONFIRM.
PG  - 1671-1679
LID - S0149-2918(17)30765-8 [pii]
LID - 10.1016/j.clinthera.2017.06.012 [doi]
AB  - PURPOSE: In Phase III studies (DEFINE [Determination of the Efficacy and Safety 
      of Oral Fumarate in Relapsing-Remitting MS]/CONFIRM [Comparator and 
      an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis]), delayed-release 
      dimethyl fumarate (DMF) demonstrated significant efficacy and a favorable 
      benefit-risk profile in patients with relapsing-remitting multiple sclerosis 
      (RRMS). Post hoc analyses of integrated data from DEFINE/CONFIRM were conducted 
      to evaluate the effect of DMF in patients previously treated with interferon 
      (IFN) beta. METHODS: Patients (age 18-55 years; Expanded Disability Status Scale 
      score, 0-5.0) were randomized to receive DMF 240 mg BID or TID, placebo, or 
      glatiramer acetate (CONFIRM only) for up to 2 years. Previous IFN users received 
      at least 1 IFN treatment >3 months before randomization. Data for DMF 240 mg BID 
      (approved dosing regimen) are reported. FINDINGS: In the integrated 
      intention-to-treat population, 172 and 169 patients receiving DMF or placebo, 
      respectively, had received >/=1 prior IFN. In this subgroup, significant reductions 
      with DMF versus placebo were observed for the annualized relapse rate (rate 
      ratio, 0.55 [95% CI, 0.40-0.77]), new/newly enlarging T2-hyperintense lesions 
      (lesion mean ratio, 0.16 [95% CI, 0.09-0.29]), odds of having more 
      gadolinium-enhancing lesions (odds ratio, 0.17 [95% CI, 0.07-0.44]), and new 
      T1-hypointense lesions (lesion mean ratio, 0.25 [95% CI, 0.14-0.45]). Median 
      Expanded Disability Status Scale scores remained stable during the study period. 
      Adverse events associated with DMF included flushing and gastrointestinal events. 
      IMPLICATIONS: In this post hoc analysis in patients with previous IFN treatment, 
      DMF demonstrated significant efficacy over 2 years versus placebo and an adverse 
      event profile consistent with the overall population of DEFINE/CONFIRM. 
      ClinicalTrials.gov identifiers: DEFINE, NCT00420212; and CONFIRM, NCT00451451.
CI  - Copyright (c) 2017 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Fernandez, Oscar
AU  - Fernandez O
AD  - Department of Neurology, Instituto de Investigacion Biomedica de Malaga, Hospital 
      Regional Universitario, Malaga University, Malaga, Spain.
FAU - Giovannoni, Gavin
AU  - Giovannoni G
AD  - Blizard Institute, Queen Mary University of London, London, United Kingdom.
FAU - Fox, Robert J
AU  - Fox RJ
AD  - Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, 
      Cleveland, Ohio.
FAU - Gold, Ralf
AU  - Gold R
AD  - St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.
FAU - Phillips, J Theodore
AU  - Phillips JT
AD  - Multiple Sclerosis Program, Baylor Institute for Immunology Research, Dallas, 
      Texas, USA.
FAU - Potts, James
AU  - Potts J
AD  - Biogen, Cambridge, Massachusetts, USA.
FAU - Okwuokenye, Macaulay
AU  - Okwuokenye M
AD  - Biogen, Cambridge, Massachusetts, USA. Electronic address: 
      macaulay.okwuokenye@biogen.com.
FAU - Marantz, Jing L
AU  - Marantz JL
AD  - Biogen, Cambridge, Massachusetts, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT00420212
SI  - ClinicalTrials.gov/NCT00451451
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20170725
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Immunosuppressive Agents)
RN  - 5M691HL4BO (Glatiramer Acetate)
RN  - 77238-31-4 (Interferon-beta)
RN  - FO2303MNI2 (Dimethyl Fumarate)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Delayed-Action Preparations/adverse effects/therapeutic use
MH  - Dimethyl Fumarate/adverse effects/*therapeutic use
MH  - Female
MH  - Glatiramer Acetate/therapeutic use
MH  - Humans
MH  - Immunosuppressive Agents/adverse effects/*therapeutic use
MH  - Interferon-beta/therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Multiple Sclerosis, Relapsing-Remitting/*drug therapy
MH  - Recurrence
MH  - Risk Assessment
MH  - Treatment Outcome
MH  - Young Adult
OTO - NOTNLM
OT  - clinical
OT  - delayed-release dimethyl fumarate
OT  - interferon beta
OT  - neuroradiological
OT  - relapsing-remitting multiple sclerosis
OT  - safety
EDAT- 2017/07/29 06:00
MHDA- 2018/02/21 06:00
CRDT- 2017/07/29 06:00
PHST- 2016/09/08 00:00 [received]
PHST- 2017/05/25 00:00 [revised]
PHST- 2017/06/23 00:00 [accepted]
PHST- 2017/07/29 06:00 [pubmed]
PHST- 2018/02/21 06:00 [medline]
PHST- 2017/07/29 06:00 [entrez]
AID - S0149-2918(17)30765-8 [pii]
AID - 10.1016/j.clinthera.2017.06.012 [doi]
PST - ppublish
SO  - Clin Ther. 2017 Aug;39(8):1671-1679. doi: 10.1016/j.clinthera.2017.06.012. Epub 
      2017 Jul 25.